Perfusate adsorption during ex vivo lung perfusion improves early post-transplant lung function

Abstract

Objective: Improvement in ex vivo lung perfusion (EVLP) protocols could increase the number of donors available for transplantation and protect the lungs from primary graft dysfunction. We hypothesize that perfusate adsorption during EVLP reconditions the allograft to ischemia-reperfusion injury after lung transplantation. Methods: Donor pig lungs were preserved for 24h at 4°C, followed by 6h of EVLP according to the Toronto protocol. The perfusate was additionally adsorbed through a CytoSorb adsorber in the treatment group, whereas control lungs were perfused according to the standard protocol (n = 5, each). EVLP physiology and biochemistry were monitored. Upon completion of EVLP, a left single lung transplantation was performed. Oxygenation function and lung mechanics were assessed during a 4-hour reperfusion period. The inflammatory response was determined during EVLP and reperfusion. Results: The cytokine concentrations in the perfusate were markedly lower with the adsorber, resulting in improved EVLP physiology and biochemistry during the 6-hour perfusion period. Post-transplant dynamic lung compliance was markedly better during the 4-hour reperfusion period in the treatment group. Isolated allograft oxygenation function and dynamic compliance were continued to be superior in the adsorber group at the end of reperfusion accompanied by a markedly decreased local inflammatory response. Conclusions: Implementation of an additional cytokine adsorber has refined the standard EVLP protocol. Furthermore, cytokine removal during EVLP improved immediate post-transplant graft function together with a less intense inflammatory response to reperfusion in pigs. Further studies are warranted to understand the beneficial effects of perfusate adsorption during EVLP in the clinical setting.

Subnormothermic Ex Vivo Lung Perfusion Temperature Improves Graft Preservation in Lung Transplantation

“…Tissue sections were stained with haematoxylin and eosin for microscopic assessment. Lung injuries were assessed according to a previously published scoring system [7].…”

Donor Death Category Is an Effect Modifier Between Cold Ischemia Time and Post-transplant Graft Function in Deceased-Donor Kidney Transplant Recipients

“…Clinical trials assessing the effects of NMP on early and longer-term graft outcomes are needed ( 38 ). In addition, absorption of proinflammatory cytokines during cold perfusion breaks the cytokine cascade and amplification; absorption during perfusion reduces the inflammatory response and improves renal blood flow and graft viability in animal models ( 39 , 40 ). It provides another means for reducing ischemia-reperfusion injury.…”

Reduction of primary graft dysfunction using cytokine filtration following acute respiratory distress syndrome in lung transplantation

“…In patients with severe sepsis and acute lung injury, the device was reported to have reduced the levels of IL-6, IL-8, IL-1β and TNF-α (28)(29)(30)(31)53). Based on the finding that the filtration is beneficial in ameliorating healthy lungs damaged by ischemia, it was then utilized in this study for its potential to rescue ARDS donor lungs for LTx (38,39).…”

“…Cytokine filtration has recently been evaluated in conjunction with EVLP in pre-clinical settings and has been able to rejuvenate healthy lungs from extended cold ischemic storage (38,39).…”